Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P. R. China.
J Mater Chem B. 2019 Jan 28;7(4):576-585. doi: 10.1039/c8tb02600a. Epub 2019 Jan 2.
The intrinsic limits of conventional cancer therapies prompt the development of a new technology for a more effective and safer cancer treatment. The bioresponsive delivery technique has recently emerged as an innovative strategy to overcome multiple barriers in the systemic delivery of nanoparticle (NP)-based therapeutics. However, some issues especially the tumor penetration-retention balance have not been completely solved, which may induce the suboptimal therapeutic effect. Herein, we developed a new multifunctional sharp pH-responsive NP platform for targeted drug delivery and effective cancer therapy. This NP platform is made of the sharp pH-responsive poly(2-(diisopropylamino)ethylmethacrylate) (PDPA) polymer as the inner core, amphiphilic lipid-poly(ethylene glycol) (lipid-PEG) as the outer shell, and the internalizing RGD (iRGD) peptide encoded on the surface. After anticancer drug loading and then systemic administration, the resulting NP platform shows the following features in one nanostructure: (i) the PEG shell to prolong blood circulation; (ii) the iRGD peptide to enhance tumor targeting and penetration; (iii) a larger particle size (∼80 nm) than that of free drug to ensure long tumor retention; (iv) the sharp endosomal pH response of the PDPA polymer to induce fast intracellular drug release and thus efficient inhibition of tumor growth. Together with facile polymer synthesis and robust NP formulation to enable easy scale-up, the multifunctional NP platform reported herein shows great potential as a new generation nanomedicine for effective cancer treatment.
传统癌症疗法的固有局限性促使人们开发出一种新技术，以实现更有效和更安全的癌症治疗。生物响应性递药技术最近作为一种创新策略出现，旨在克服基于纳米粒子（NP）的治疗剂系统递药中的多种障碍。然而，一些问题，特别是肿瘤穿透-保留平衡问题，尚未得到完全解决，这可能导致治疗效果不理想。在此，我们开发了一种新的多功能尖锐 pH 响应性 NP 平台，用于靶向药物输送和有效的癌症治疗。该 NP 平台由尖锐 pH 响应性聚（2-（二异丙基氨基）乙基甲基丙烯酸酯）（PDPA）聚合物作为内核，两亲性脂质-聚乙二醇（lipid-PEG）作为外壳，以及表面编码的内化 RGD（iRGD）肽组成。在载药后进行系统给药后，所得的 NP 平台在一个纳米结构中表现出以下特征：（i）PEG 壳以延长血液循环；（ii）iRGD 肽增强肿瘤靶向和穿透；（iii）比游离药物更大的粒径（约 80nm），以确保肿瘤的长时间保留；（iv）PDPA 聚合物的尖锐内涵体 pH 响应诱导快速的细胞内药物释放，从而有效抑制肿瘤生长。多功能 NP 平台易于进行聚合物合成和稳健的 NP 配方，易于放大规模，具有作为新一代用于有效癌症治疗的纳米医学的巨大潜力。
